BACKGROUND & AIMS: :Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

背景与目标： ：通过免疫组织化学法构建组织微阵列（TMA）以有效表征乳腺中大量非侵袭性上皮病变的方法是一种有吸引力的研究方法，但也带来了技术挑战。我们报告进行的方法学研究，以优化从大型乳腺癌病例对照研究中收集的无创乳腺组织中构建TMA的方法。我们使用直径为2.0毫米针头的手动排列技术，从32位乳腺癌女性的标本中构建了TMA，这些标本包括以下目标：（1）28个末梢小叶单位（TDLU）； （2）28例原位导管癌，（3）23例浸润性癌。通过精心选择目标，我们通过TMA第30节实现了约80％的非侵入性目标的代表，并得到了持续的保护。 TDLU靶标的免疫组织化学染色显示，在30.8％的肾小管中，雌激素受体（ER）阳性染色，在50.0％中，孕激素受体（PR）染色阳性。为了建立一种有效的方法来评估TDLU中的染色结果，我们创建了一个分类评分系统，以估计含有阳性染色细胞的小管的百分比（<10％，10％至5​​0％，>或= 50％），并比较结果与那些通过肾小管计数获得的。两种方法之间的比较表明，ER染色的70.8％和PR染色的79.2％完全吻合，没有两类差异。单个区域中相同组织类型（TDLU或DCIS）的多个（多达4个）非侵入性靶标中的ER / PR表达水平显示出良好的相关性。这些数据表明，尽管精心选择了靶标，但生产无创性乳房结构的TMA是可行的，并且此类核心的免疫染色可允许对肿瘤周围组织进行有效的免疫组织化学表征。需要对该方法进行其他探索。

BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌症疼痛患者中吗啡连续静脉输注（CIVI）与吗啡连续皮下输注（CSCI）的剂量，疗效和副作用。符合条件的患者被转到姑息治疗计划，并接受稳定剂量的吗啡CIVI。该设计是患者内部的单向交叉。其中每个患者提供了从吗啡从CIVI切换到CSCI之前和之后的数据。 “救援”剂量是根据需要每2小时给予的每小时剂量的50％。吗啡通过McGaw / AccuPro容量输注泵静脉内（i.v.）和皮下（s.c.）输注。获得包括副作用和疼痛评估在内的基线数据后，每天对患者进行两次毒性和止痛效果评估。连续48个小时具有稳定CIVI剂量的患者以与静脉内（i.v.）阶段相同的剂量转入CSCI。稳定剂量定义为无剂量变化，在过去24小时内有四个或更少的急救剂量，疼痛等级为无或轻度。如果连续96个小时保持这些标准，则认为CIVI等于CSCI。入组患者57例，其中40例可评估（女性15例，男性25例）。中位年龄为67岁（范围为30-83岁）。在整个静脉内维持稳定剂量后，所有40位参与者阶段，跨到南卡罗来纳州相并保持在s.c.至少持续48小时。在整个静脉内，有32名患者维持了稳定的剂量。和s.c.阶段。平均稳定i.v.剂量（第2天）为5.05 mg / hr，平均稳定s.c.剂量（第4天）为5.7 mg / hr（P = 0.01）。第2天的平均急救剂量为每24小时0.83，而第4天为每24小时0.80（P = 0.6）。第2天的平均类别疼痛评分为0.83，第4天的平均疼痛评分为0.85（P = 0.7）。第2天的平均视觉模拟量表（VAS）为22.9毫米，而第4天为17.6毫米（P = 0.1）。第2天的副作用的平均发生率为1.7，而第4天的平均发生率为2.0（P = 0.2）。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点的局部毒性（轻度红斑）的报道，需要进行部位改变。我们所有的40名患者均通过CIVI和CSCI吗啡可以很好地控制疼痛。在没有保持相同i.v.的八位参与者中和s.c.剂量较高时，所有患者均具有足够的疼痛控制能力，并且在较高的s.c.下具有相似的副作用。吗啡剂量。这些数据表明和s.c.当以连续输注方式给药时，对于大多数患者而言，这两种途径均具有镇痛作用。疼痛控制和副作用状况非常相似且可以接受。南卡罗来纳州吗啡是静脉注射的绝佳替代品。需要胃肠外吗啡治疗的住院患者和门诊患者中的吗啡疼痛。

BACKGROUND & AIMS: :Extensive literatures have shown significant trend of progressive electrical changes according to the proliferative characteristics of breast epithelial cells. Physiologists also further postulated that malignant transformation resulted from sustained depolarization and a failure of the cell to repolarize after cell division, making the area where cancer develops relatively depolarized when compared to their non-dividing or resting counterparts. In this paper, we present a new approach, the Biofield Diagnostic System (BDS), which might have the potential to augment the process of diagnosing breast cancer. This technique was based on the efficacy of analysing skin surface electrical potentials for the differential diagnosis of breast abnormalities. We developed a female breast model, which was close to the actual, by considering the breast as a hemisphere in supine condition with various layers of unequal thickness. Isotropic homogeneous conductivity was assigned to each of these compartments and the volume conductor problem was solved using finite element method to determine the potential distribution developed due to a dipole source. Furthermore, four important parameters were identified and analysis of variance (ANOVA, Yates' method) was performed using design (n = number of parameters, 4). The effect and importance of these parameters were analysed. The Taguchi method was further used to optimise the parameters in order to ensure that the signal from the tumour is maximum as compared to the noise from other factors. The Taguchi method used proved that probes' source strength, tumour size and location of tumours have great effect on the surface potential field. For best results on the breast surface, while having the biggest possible tumour size, low amplitudes of current should be applied nearest to the breast surface.

背景与目标： ：大量文献显示，根据乳腺上皮细胞的增殖特性，进行性电变化的显着趋势。生理学家还进一步假设，恶性转化是由于持续的去极化和细胞分裂后细胞无法重新极化所致，因此与非分裂或静止状态的癌症相比，癌症发展的区域相对去极化了。在本文中，我们提出了一种新的方法，即Biofield Diagnostic System（BDS），它可能具有增强乳腺癌诊断过程的潜力。该技术基于分析皮肤表面电势以鉴别诊断乳房异常的功效。我们通过将乳房视作处于仰卧状态的半球，且各层厚度不相等，从而开发出了接近实际的女性乳房模型。各向同性的电导率分配给这些隔室中的每一个，并使用有限元方法解决了体积导体问题，以确定由偶极子源产生的电势分布。此外，确定了四个重要参数，并使用设计进行了方差分析（ANOVA，Yates方法）（n =参数数量4）。分析了这些参数的作用和重要性。 Taguchi方法进一步用于优化参数，以确保与其他因素产生的噪声相比，来自肿瘤的信号最大。使用的Taguchi方法证明了探针的源强度，肿瘤大小和肿瘤位置对表面电势场有很大的影响。为了在乳腺表面获得最佳效果，同时应尽可能增大肿瘤的大小，应在最靠近乳腺表面的地方施加较小的电流。

BACKGROUND & AIMS: :In this review, we focused on our studies of cancer dormancy in a murine B cell lymphoma and human breast cancer. Lifelong dormancy was induced in syngeneic mice by prior immunization to the idiotype of the tumor cell (TC) Ig before TC challenge. The mice maintained approximately 10(6) lymphoma cells in their spleen throughout their lifetime despite replication of the TCs at a reduced rate. Recurrences occurred randomly. Because of the balance between replication and cell death, we hypothesized that a similar balance might occur in long-term survivors of breast cancer when the risk of recurrences is very low. We developed a sensitive assay for circulating tumor cells (CTCs) which none were found in normal age-matched women. One third of patients, 7-22 years after mastectomy and without any evidence of disease, had CTCs. The half-life of these CTCs could be deduced from other studies as probably 2-3 hours. Hence, there was a precise balance between replication of TCs (presumably from micrometastases) and cell death. Therefore, a major population of clinically cured breast cancer patients have a chronic disease controlled by their own physiological mechanisms. We speculate on underlying mechanisms based both on studies in experimental models and clinical trials.

背景与目标： ：在这篇综述中，我们集中于对小鼠B细胞淋巴瘤和人类乳腺癌的癌症休眠研究。通过在TC攻击之前先对肿瘤细胞（TC）Ig的独特型进行免疫，可以在同系小鼠中终生休眠。尽管TCs的复制率降低了，但小鼠的一生中仍在脾脏中维持着约10（6）个淋巴瘤细胞。复发随机发生。由于复制和细胞死亡之间的平衡，我们假设当复发风险非常低时，长期存活的乳腺癌患者可能会发生类似的平衡。我们开发了一种循环肿瘤细胞（CTC）的灵敏检测方法，在正常年龄的女性中均未发现。乳房切除术后7-22年且无任何疾病证据的三分之一患者患有CTC。这些CTC的半衰期可以从其他研究中推断出来，大概为2-3小时。因此，在TC的复制（可能来自微转移）和细胞死亡之间存在着精确的平衡。因此，大部分临床治愈的乳腺癌患者患有受其自身生理机制控制的慢性疾病。我们基于实验模型和临床试验研究潜在的机制。

BACKGROUND & AIMS: Prostate-specific antigen (PSA), a glycoprotein initially thought to be produced only by the epithelial cells of the prostate, has recently been found in 30% of female breast tumours using immunofluorometry. Our aim was to localize PSA immunohistochemically in a selected group of 27 paraffin-embedded breast tissues. A scoring system was developed for the histological assessment of PSA positivity within the breast tissue. One pathologist (DH) scored, classified and graded all tumours. Site-specific PSA staining was noted in the histology slides. Intense staining was identified in apocrine metaplasia and within the lining ductal epithelium of cystically dilated ducts. The epithelium in lesions of sclerosing adenosis was also frequently positive for PSA staining. Hyperplastic ductal epithelium (especially of mild degree) occasionally stained positive, as did normal breast ducts. Better differentiated tumours showed PSA staining [e.g. mucinous carcinoma (colloid)]. If an infiltrating duct carcinoma showed staining for PSA, adjacent intraductal carcinoma was also noted to stain positively, if present.

背景与目标： 前列腺特异性抗原（PSA）是一种最初被认为仅由前列腺上皮细胞产生的糖蛋白，最近在30％的女性乳腺肿瘤中使用免疫荧光法发现了这种蛋白。我们的目标是通过免疫组织化学方法将PSA定位在27个石蜡包埋的乳腺组织中。开发了评分系统用于乳腺组织内PSA阳性的组织学评估。一名病理学家（DH）对所有肿瘤进行了评分，分类和分级。组织学幻灯片中记录了位点特异性PSA染色。在顶泌化生和囊性扩张管的衬里导管上皮中鉴定到强染色。硬化性腺病病灶中的上皮也常对PSA染色呈阳性。增生性导管上皮（尤其是轻度导管）偶尔染色为阳性，正常乳腺导管也是如此。分化更好的肿瘤表现出PSA染色[例如粘液癌（胶体）]。如果浸润性导管癌显示PSA染色，则也可以发现邻近的导管内癌也呈阳性染色。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： ：据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了低氧刺激是否影响基质和胰腺癌细胞。我们的研究结果表明，缺氧显着提高了胰腺癌（PK8）和成纤维细胞（MRC5）中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用由低氧MRC5细胞制备的条件培养基（低氧条件培养基）培养低氧PK8细胞时，侵袭性进一步加快。在缺氧条件下，PK8细胞中的MMP-2，MMP-7，MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子（HGF）分泌，这导致PK8细胞中c-Met磷酸化的升高。相反，通过从低氧条件培养基中除去HGF，可以降低PK8细胞的癌浸润，MMP活性和c-Met磷酸化升高。在免疫组织化学研究中，在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达，因此表明在癌细胞和基质细胞中均存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统，从而促进了胰腺癌的侵袭性侵袭性特征。

BACKGROUND & AIMS: :Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.

背景与目标： ：尽管在对抗胃癌方面取得了长足的进步，但它仍然是由特殊的组织学和分子学特征定义的复杂致死性疾病。本研究的目的是研究pRb2 / p130，VEGF，EZH2，p53，p16（INK4A），p27（KIP1），p21（WAF1），Ki-67的表达，并分析它们与临床病理因素的可能关系。通过免疫组织化学检查了47例患者的表达模式，其中27例为肠型，20例为弥散型，平均随访56个月，并通过Western blot检测AGS，N87，KATO-III和YCC-2 ，-3，-16个胃细胞系。总体而言，胃癌显示EZH2与高水平的p53，Ki-67和细胞质pRb2 / p130相关（分别为P <0.05和P <0.01）。在肠型中发现EZH2表达增加，并且与远处转移的风险相关（分别为P <0.05和P <0.01），表明该蛋白可能在这种类型的癌症中具有预后价值。有趣的是，观察到p27（KIP1）表达水平与晚期疾病和转移的风险之间存在强烈的负相关（P <0.05），而p21（WAF1）和低度胃癌（G1）的表达水平之间呈正相关。肿瘤（P <0.05），证实了这些肿瘤抑制基因在胃癌中的传统接受作用。最后，在核pRb2 / p130的表达水平与低度（G1）胃肿瘤的表达水平之间发现了直接相关性，具有统计学意义（P <0.05）。总之，这些数据可能有助于进一步阐明与两种主要胃癌组织学类型及其侵袭潜能有关的致病机制。

BACKGROUND & AIMS: :A retrospective study of male breast cancer was undertaken at Ouagadougou University Teaching Hospital over a 3 year period (1993-1996). Authors report 5 cases representing 4.16% of all breast cancers. The patients' mean age was 61 years. The average duration of signs and symptoms before the diagnosis was 13 months. Clinically all the 5 cases presented advanced cancers (4 T4N2M0, 1 T4N2M1 according to UICC TNM System) with size ranging from 5.5, to 11.5 cm. Histology found: 2 medullary infiltrating carcinoma, 1 canalar infiltrating carcinoma, 1 colloid mucous carcinoma and 1 lobular infiltrating carcinoma. All patients had mastectomy associated with axillary clearance in 4 cases. Radiotherapy, chemotherapy and hormonotherapy were not associated because unavailable in Burkina Faso. Three patients died: the first, 10 days after surgical treatment and the 2 others respectively after 14 and 17 months. We have lost sight 1 patients. The last one is still alive. Authors find that to get better prognosis, it is important to improve medical and technical means, to increase information and to promote early detection.

背景与目标： ：在瓦加杜古大学教学医院进行了为期3年（1993年至1996年）的男性乳腺癌回顾性研究。作者报告了5例病例，占所有乳腺癌的4.16％。患者的平均年龄为61岁。诊断前平均体征和症状持续时间为13个月。临床上，所有5例患者均出现晚期癌（根据UICC TNM System，4例T4N2M0、1例T4N2M1），大小在5.5至11.5厘米之间。组织学发现：2个髓样浸润癌，1个管状浸润癌，1个胶体粘​​液癌和1个小叶浸润癌。所有患者均进行了伴有腋窝清除术的乳房切除术4例。放疗，化学疗法和激素疗法没有联系，因为布基纳法索无法使用。 3例患者死亡：第一例，手术治疗10天后死亡，另外2例分别在14个月和17个月后死亡。我们失去了视力1例患者。最后一个还活着。作者发现，要获得更好的预后，重要的是改善医学和技术手段，增加信息并促进早期发现。

BACKGROUND & AIMS: :Several attempts to classify gastric cancer (GCA) have been made over the past decades. Most successful, and widely used, is the classification by Laurén, which distinguishes, by microscopical morphology alone, two main cancer pathogeneses, diffuse (DGCA) and intestinal (IGCA) subtypes, which appear clearly as dissimilar clinical and epidemiological entities. Here we review the main differences in epidemiology, histopathology, and molecular pathology of the two main subtypes of gastric carcinomas based on Laurén classification. In clinical practice, however, clinical staging, particularly in predicting the survival, still remains superior to all classifications of gastric cancer independent of cancer type. The existence of local precursor lesions or conditions of IGCA tumours, i.e. Helicobacter pylori gastritis, atrophic gastritis (AG), intestinal metaplasia (IM), adenoma, dysplasia, and intramucosal neoplasia, is firmly established. The links of DGCA with intestinal-type epithelium, AG or IM are poor, or do not exist. So far, H. pylori gastritis is the only universal precursor condition for DGCA. It implies that AG and achlorhydria are of minor significance and infrequent in the development of DGCA but are important steps in that of IGCA. Despite an increasing body of data, the overall view on molecular pathology of GCA remains fragmentary. No consistent differences in the molecular pathology of GCA subtypes to meet the Laurén classification have been established. With the exception of TP53, no gene mutation occurring regularly in both histological types of GCA has been reported. Chromosomal aberrations and loss of heterozygosity seem to be non-specific and do not follow any consistent route in the progression of GCA. Microsatellite instability is more commonly found in IGCA than in DGCA. The present epigenetic data suggest that most of the decrease (or loss) of gene expression may be explained by promoter hypermethylation which is more often found in IGCA. In DGCA specific genes such as CDH1 are more often hypermethylated. Compared with GCA, in premalignant condition lesions gene mutations and chromosomal aberrations are infrequent. Epigenetic dysregulation might also represent a major mechanism for altered gene expression in premalignant stages in gastric carcinogenesis.

背景与目标： ：在过去的几十年中，已经进行了多次尝试来对胃癌（GCA）进行分类。最成功且应用最广泛的是Laurén的分类法，该分类法仅通过显微镜形态就可以区分出两种主要的癌症病原体，即弥散（DGCA）和肠道（IGCA）亚型，它们明显表现为不同的临床和流行病学实体。在这里，我们基于Laurén分类，回顾了两种主要胃癌亚型的流行病学，组织病理学和分子病理学的主要差异。然而，在临床实践中，临床分期，尤其是在预测存活率方面，仍然优于胃癌的所有分类，而与癌症类型无关。牢固地确定了局部局部前体病变或IGCA肿瘤的状况，即幽门螺杆菌胃炎，萎缩性胃炎（AG），肠化生（IM），腺瘤，异型增生和粘膜内瘤变。 DGCA与肠型上皮，AG或IM的联系较差或不存在。到目前为止，幽门螺杆菌胃炎是DGCA的唯一通用先兆病状。这表明AG和胃酸缺乏症在DGCA的发展中意义不大，很少出现，但在IGCA中是重要的步骤。尽管有越来越多的数据，但关于GCA分子病理学的整体观点仍是零碎的。尚未建立符合劳伦分类的GCA亚型分子病理学方面的一致差异。除TP53外，在两种组织学类型的GCA中均没有定期发生基因突变的报道。染色体畸变和杂合性丧失似乎是非特异性的，并且在GCA的发展过程中未遵循任何一致的途径。在IGCA中比在DGCA中更常见微卫星不稳定性。目前的表观遗传学数据表明，基因表达的大多数减少（或丧失）可以通过在IGCA中更常见的启动子高甲基化来解释。在DGCA中，诸如CDH1之类的特定基因更经常被甲基化。与GCA相比，在癌变前病灶中，基因突变和染色体畸变很少见。表观遗传失调也可能代表了胃癌发生前癌变阶段基因表达改变的主要机制。

BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

背景与目标： 背景：我们检查了膀胱癌中P53基因的杂合性（LOH）缺失，并研究了P53基因在乳头状瘤恶性进展中的作用。另外，检查了复发性膀胱癌的克隆性。
方法：分析了47例患者的67例膀胱癌中P53基因的LOH。从福尔马林固定，石蜡包埋的组织中提取DNA，在P53基因的3个多态性位点处通过聚合酶链反应（PCR）进行扩增，并通过非放射性同位素单链构象多态性（Non-RI SSCP）分析。
结果：在40个信息量样本中，在13个样本中检测到LOH，其中3个7级中有4个（57％），2个23级中有9个（39％），1个10级中没有10个（10％）。在1级和2级以及1级和3级的LOH之间观察到统计学意义。对5例恶性进展的分析表明，3例（60％）在原发性肿瘤中显示LOH，2例在复发性肿瘤中显示LOH。 ，与LOH在19例（16％）的3例中未显示出恶性进展的情况相反。 4例异时复发表现为LOH。在复发性肿瘤中2个，仅在初始肿瘤中1个，在两个肿​​瘤中1个。
结论：P53基因的改变被认为与肿瘤的分级有关，并有助于膀胱癌的恶性进展。 P53基因中的LOH可作为浅表性膀胱癌预后的临床指标。

BACKGROUND & AIMS: :The course of untreated localized prostate cancer after 10 years of follow-up is at large unknown. As curative treatment is usually only offered patients with a life expectancy exceeding 10 Years, the expected course of the disease if left untreated is of the utmost interest. This paper aims to describe the outcome for patients who survive for more than 10 years when treated without curative intent. The results indicate that cancer specific mortality in patients with localized prostate cancer increases steadily over time and is approximately 50% after 15 years. This is a much higher figure than in reported series on radical prostatectomy. Even if many deaths occur at an old age, prostate cancer death is shown to be associated with a significant morbidity, need for palliative treatment, hospital care and cost. Preventing prostate cancer death is therefore not only a matter of saving year of life but also to prevent suffering caused by the disease. Modern diagnostic tools, such as prostate specific antigen, seem to detect clinically significant cancers in the vast majority of patients. Over diagnosis seems to be uncommon if diagnostic procedures are restricted to patients with a long life expectancy. Localized prostate cancer is a slow-growing but progressive neoplastic disease. When diagnosed in a man with a longer life expectancy it should be handled as such.

背景与目标： ：十年随访后未经治疗的局限性前列腺癌的病程目前还不得而知。由于通常仅为预期寿命超过10年的患者提供治愈性治疗，因此，如果不及时治疗，预期的病程将是最重要的。本文旨在描述未经治疗而存活超过10年的患者的预后。结果表明，局部前列腺癌患者的癌症特异性死亡率随时间稳定增加，并且在15年后约为50％。这是一个比已报道的前列腺癌根治术系列高得多的数字。即使许多死亡发生在老年，前列腺癌的死亡也被证明与明显的发病率，姑息治疗的需要，医院护理和费用有关。因此，预防前列腺癌的死亡不仅是挽救生命的一年，而且是预防由该疾病引起的痛苦的问题。现代诊断工具，例如前列腺特异性抗原，似乎可以在绝大多数患者中检测出具有临床意义的癌症。如果诊断程序仅限于预期寿命较长的患者，则过度诊断似乎不常见。局限性前列腺癌是一种生长缓慢但正在进行的肿瘤性疾病。当诊断为预期寿命较长的男性时，应照此处理。

BACKGROUND & AIMS: :In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.

背景与目标： ：在先前针对胰腺癌中差异表达基因的大规模筛选中，我们鉴定了在癌症中高度过表达的基因，该基因编码具有四个K同源（KH）域的新型蛋白质。 KH结构域存在于RNA结合蛋白的子集中，包括前mRNA结合（hnRNP）K蛋白和脆弱的X智力低下基因产物（FMR1）。通过荧光原位杂交（FISH），将鉴定出的名为koc（在癌症中过表达的KH域蛋白）的基因分配给7p11.5染色体。两个假基因位于6号和11号染色体上。克隆的koc cDNA具有250 bp的5'-UTR，1740 bp的ORF和2168 bp的3'-UTR。富含AU的3'非翻译区域的koc包含八个AUUUA和四个AUUUUUA重复的基序。推导的具有580个氨基酸的koc蛋白的相对分子质量（Mr）约为65,000（65 K）。与正常胰腺和慢性胰腺炎组织相比，koc转录本在胰腺癌细胞系和胰腺癌组织中高度过表达。在其他人类肿瘤的组织样本中也发现了高水平的表达。由于已经显示出KH结构域参与RNA合成和代谢的调节，我们推测koc可能通过干扰转录和/或转录后过程而在调节肿瘤细胞增殖中发挥作用。但是，koc在人肿瘤细胞中的确切作用尚不清楚，尚待阐明。

BACKGROUND & AIMS: :A prospective collection of positive antimicrobial cultures was performed over 12 consecutive months in the medical intensive care unit of a cancer hospital. In all, 144 infections and 163 pathogens were documented during 87 of the 528 admissions. Lung, urinary, ENT (ear, nose and throat) infections and bacteraemia were the most frequently documented. Staphylococcus species, Streptococcus species, Escherichia coli, Klebsiella species and Pseudomonas species were the most common pathogens. Gram-positive strains were observed predominantly during monomicrobial bacteraemia (48.9%). Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were found in 58% and 92% of the isolated strains respectively. No particular outbreak was identified. A further prospective study will be necessary to evaluate the impact of the antibiotic use on the selection of resistant strains in our ICU.

背景与目标： ：在癌症医院的医疗重症监护室连续12个月进行了前瞻性抗菌药物阳性培养。在528例入院病例中，总共记录了144例感染和163种病原体。肺，尿，耳鼻喉（耳，鼻，喉）感染和菌血症的记录最频繁。葡萄球菌，链球菌，大肠杆菌，克雷伯菌和假单胞菌是最常见的病原体。革兰氏阳性菌株主要在单微生物菌血症期间观察到（48.9％）。分别在58％和92％的分离菌株中发现了耐甲氧西林的金黄色葡萄球菌（MRSA）和表皮葡萄球菌（MRSE）。没有发现特定的爆发。有必要进行进一步的前瞻性研究，以评估抗生素使用对我们ICU中耐药菌株选择的影响。

BACKGROUND & AIMS: OBJECTIVE:To examine the relationships between the expression of protein Nm23 and surgical stage, histologic grade, histopathologic findings, and survival in women with endometrial carcinoma. METHODS:19 patients with lymph node involvement were matched with 24 patients without lymph node involvement and the best paraffin-embedded blocks were selected for Nm23 immunohistochemical staining. The slides were evaluated semiquantitatively according to their degree of cytoplasmic staining. Statistical analysis was performed to determine whether there was a relationship between Nm23 expression and surgical stage, histologic grade, depth of myometrial invasion, lymph node metastasis, and/or lymphovascular space involvement. Survival analysis was also performed. RESULTS:Slides from 15 patients (79%) with lymph node involvement and 22 patients (88%) without lymph node involvement were found to be positive for Nm23 (P=0.01). No significant relations were observed between Nm23 expression and surgical stage, histologic grade, depth of myometrial invasion, or lymphovascular space involvement. Nm23 expression was found to be significantly related to lower rates of lymph node metastasis and longer survival (P=0.02). CONCLUSION:Elevated Nm23 expression is related to lower rates of lymph node metastasis and longer survival.

背景与目标： 目的：探讨Nm23蛋白的表达与子宫内膜癌女性手术分期，组织学分级，组织病理学发现及生存之间的关系。
方法：将19例淋巴结受累患者与24例无淋巴结受累患者进行配对，并选择最佳石蜡包埋块进行Nm23免疫组化染色。根据细胞质染色的程度对玻片进行半定量评估。进行统计分析以确定Nm23的表达与手术分期，组织学分级，肌层浸润深度，淋巴结转移和/或淋巴管间隙受累之间是否存在关系。还进行了生存分析。
结果：发现淋巴结受累的15例患者（79％）和未淋巴结受累的22例患者（88％）的玻片Nm23阳性（P = 0.01）。 Nm23表达与手术分期，组织学分级，肌层浸润深度或淋巴管间隙受累之间无显着相关性。发现Nm23表达与较低的淋巴结转移率和更长的存活率显着相关（P = 0.02）。
结论：Nm23表达升高与淋巴结转移率降低和生存期延长有关。

BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.

背景与目标： ：寻找新的癌症药物靶标的主要问题是该药物通常对正常组织有毒性，需要高剂量才能杀死肿瘤细胞。因此，细胞靶标似乎涉及对癌症治疗的低剂量反应，因此特别令人感兴趣，因为它们可以选择性地靶向未被治疗靶标的正常组织，因此可能引起令人不快的副作用，或者可能适合于剥削以改善治疗效果。治疗比率。辐射诱导的旁观者效应[RIBE]是本综述的主题之一，该效应导致在未辐射的细胞中观察到辐射样反应。 RIBE是一种新现象，表明在低剂量时，细胞信号传导比直接DNA损伤更为重要。从历史上看，DNA一直被认为是放射治疗的目标。人们日益认识到信号转导很重要，这开启了几种重要的治疗策略，本文将对此进行讨论。 RIBE似乎是组织或细胞中普遍的应激反应的结果，这种应激反应是在组织，器官或生物体的水平而不是单个细胞的水平表达的。信号可能由所有暴露的细胞产生，但响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET（X射线或γ射线）辐射暴露的主要反应是死亡反应。这具有许多细胞凋亡特征，但尽管在许多肿瘤细胞系中死亡反应受到抑制，但在没有p53表达的细胞系中可能检测到。虽然在肿瘤周围未辐射的正常细胞中的死亡反应似乎是不利的，但实际上可以起到保护作用，并从群体中清除受损的细胞。如果利用得当，它可能会导致开发新药物，其目的不是破坏组织，而是使稳态机制能够控制肿瘤的扩展。在这种情况下，有害或有益反应的水平将与细胞群体所携带的背景损伤以及决定对损伤的反应的遗传程序有关。当试图预测涉及放射线和其他细胞毒剂的混合疗法的后果时，这一重点可能很重要。在这篇综述中，我们对电离辐射诱发旁观者效应的潜在机制的现有知识进行了综述，并探讨了如何利用旁观者效应来生产旨在稳定组织稳态而不是稳定组织的新一代抗癌药物的问题。考虑组织破坏。